Our broad objective is to study the mechanisms by which deoxyhemoglobin S forms a fibrous birefringent gel at certain concentrations and temperatures. We are not directly concerned with the sickling of erythrocytes but rather with the underlying relations between the tendency of purified HbS to gel, and its structure and relevant physico-chemical properties. The emphasis in this work will continue to be on events which occur during a latent period before the sudden increase in viscosity, which terminates in the formation of a fibrous gel. This pre-gelation stage is strongly affected by both temperature and the concentration of hemoglobin and may exceed 14 hours. The proposed work is largely a continuation and extension of our current work, which comprises a systematic study of the rates and equilibria governing the aggregation of deoxy HbS into gels, - as determined by changes in the following properties among others: (1) Viscosity unde low shear (indication of molecular volume, shape and/or solvation). (2) Light-scattering (Raleigh scattering). Indications of size and shape. Use of homogenized gels. (3) Relaxation of transient electric birefringence. Polarizability; also changes in the rotational diffusion constant and thus molecular size and shape. (4) Interactions that occur between deoxy HbS, which is essential to the formation of gels, and other liganded forms of both A and S hemoglobins. These interactions diminish the minimum gelling concentration of deoxy S although they always require a higher total hemoglobin concentration. (5) Differences in the kinetics of the dissociation of oxygen and carbon monoxide by the normal and mutant hemoglobins. Such effects give information about differences in the heme environment of A and S proteins. No clinical trials or applications are planned. Nevertheless the results may be relevant to the etiology of crisis.